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| Status |
Public on Jan 01, 2021 |
| Title |
Epithelial response to IFN-γ promotes SARS-CoV-2 infection |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
SARS-CoV-2, the agent causing COVID-19, invades epithelial cells, including those of the respiratory and gastrointestinal mucosa, using angiotensin-converting enzyme-2 (ACE2) as a receptor. Subsequent inflammation can promote rapid virus clearance. However, severe cases of COVID-19 are characterized by an inefficient immune response that fails to clear infection. Using primary epithelial organoids from the colon, we explored how IFN-γ, a central antiviral mediator elevated in COVID-19, affects differentiation, ACE2 expression, and infectivity with SARS-CoV-2. ACE2 is mainly expressed by surface enterocytes of mouse and human colon. Inducing enterocyte differentiation in organoid culture resulted in increased ACE2 production. IFN-γ treatment promoted differentiation into mature KRT20+ enterocytes expressing high levels of ACE2. Similarly, IFN-γ promoted expression of ACE2 in human primary lung cells. IFN-y driven differentiation increased susceptibility to SARS-CoV-2 infection and electron microscopy revealed that the virus can efficiently complete its full life cycle in IFN-γ-treated enterocytes. Furthermore, infection-induced epithelial interferon signaling promoted enterocyte maturation and enhanced ACE2 expression. We reveal a mechanism by which IFN-y-driven inflammatory responses may increase susceptibility to SARS-CoV-2 and promote its replication.
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| Overall design |
Microarray experiments were performed as dual-color hybridizations on custom whole genome human 8 × 60K multipack microarrays (Agilent-048908). To compensate for dye-specific effects, a dye-reversal color-swap was applied.
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| Contributor(s) |
Sigal M, Heuberger J, Trimpert J, Osterrieder N, Meyer TF, Mollenkopf H |
| Citation(s) |
33544398 |
| |
| Submission date |
Aug 20, 2020 |
| Last update date |
Apr 06, 2021 |
| Contact name |
Hans-Joachim Mollenkopf |
| E-mail(s) |
mollenkopf@mpiib-berlin.mpg.de
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| Phone |
+49 30 28460 482
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| Organization name |
Max-Planck-Institute for Infection Biology
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| Lab |
Microarray/Genomics Core Facility
|
| Street address |
Charitéplatz 1
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| City |
Berlin |
| ZIP/Postal code |
10117 |
| Country |
Germany |
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| Platforms (1) |
| GPL21272 |
Agilent-048908 8x60K whole genome incl V1-V2 linc BioVacSafe final 048908 [Feature Number version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA658319 |
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